EP0474800B1 - Eye-drop - Google Patents

Eye-drop Download PDF

Info

Publication number
EP0474800B1
EP0474800B1 EP91903310A EP91903310A EP0474800B1 EP 0474800 B1 EP0474800 B1 EP 0474800B1 EP 91903310 A EP91903310 A EP 91903310A EP 91903310 A EP91903310 A EP 91903310A EP 0474800 B1 EP0474800 B1 EP 0474800B1
Authority
EP
European Patent Office
Prior art keywords
mass
primycin
eye
pyrrolidon
drop
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP91903310A
Other languages
German (de)
French (fr)
Other versions
EP0474800A1 (en
Inventor
Anna Z.Szabo
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chinoin Private Co Ltd
Original Assignee
Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt filed Critical Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt
Priority to AT91903310T priority Critical patent/ATE99947T1/en
Publication of EP0474800A1 publication Critical patent/EP0474800A1/en
Application granted granted Critical
Publication of EP0474800B1 publication Critical patent/EP0474800B1/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears

Definitions

  • the invention relates to a stable aqueous solution containing as active ingredient primycin.
  • Subjects of the present invention are further therapeutical compositions prepared from the stable aqueous solution.
  • Primycin is a macrolide antibiotic agent, which is characterized in the literature (J. Chem. Soc. Perkin I. 1974, p. 816) by a single formula: /5-(18-( ⁇ -D-arabinofuranosyloxy)-2-butyl-3,7,11,15,19,21,23,25,27-nonahydroxy-4,16,32,34-tetramethyl-1-oxo-oxacyclohexatriakonta-16,32-diene-35-yl-)/4-hydroxyhexyl/guanidium-sulphate.
  • the above literature describes its structure by a single formula, it is known, that it is an antibiotic-mixture consisting of several components (Hungarian Applications No. 2125/84 and 2869/84).
  • Primycin is a natural antibiotic agent originating from the fungal strain culture Thermopolyspora ndnsis, its preparation via fermentation is described in the Hungarian Patent Specification No. 153.593. Primycin is an antibiotic agent of a large spectrum, and it is firstly effective against gram positive bacteria and against polyresistent humanpathogenic strains too.
  • Primycin can be effectively applied for the treatment of epithelium lesions, in the urology, surgery, gynecology, dermatology, in the case of household lesions and for the treatment of burns respectively.
  • primycin is a very effective antibiotic, its therapeutical utilization was made extraordinarily difficult since it is practically insoluble in water. Thus, several efforts had earlier been made to eliminate these difficulties and to prepare pharmaceutical compositions containing primycin in a therapeutically well utilizable form while maintaining its efficiency as a whole.
  • the Hungarian Patent Specification No. 173.708 publishes heterocolloidal therapeutical compositions containing primycin. Their disadvantage is the low primycin content (0.2-1.0 %). Further the ethyl alcohol used for the preparation of the heterocolloidal solution has in some cases skin irritating effect and in the case the alcohol is vaporized from the treated surface one part of the primycin is running down from the skin without exerting a biological effect. This formulation cannot be used to prepare eye-drops.
  • the Hungarian Patent Specification No. 194.493 describes a basic gel containing primycin and N-methyl-pyrrolidon from which therapeutical compositions and different gels were prepared.
  • This composition having a gel consistency is useful to incorporate the active ingredient practically in all qalenic forms such as ointments, creams or foams, however it is not useful to prepare eye-drops.
  • the aim of our invention was to prepare a stable aqueous solution containing primycin as active ingredient, which is free from alcohol and does not contain eye-irritating substances and this way it is suitable for the preparation of eye-drops.
  • the invention relates to eye-drops characterized by, that they contain 0,02 - 0,1 mass % of primycin, 15,0 - 25,0 mass % of pyrrolidon, 12,0 - 25,0 mass % of polyoxyethylene-660-hydroxystearate, 1,0 - 5,0 mass % of polyvinyl-pyrrolidon and distilled water needed to complete to 100 mass %.
  • the eye-drops according to the invention are prepared in a way, that primycin is dissolved by heating in pyrrolidon-2 (Soluphor P R ) and to the warm solution the polyoxyethylene-660-hydroxystearate (Solutol HS 15 R ) and polyvinyl-pyrrolidon are added.
  • pyrrolidon-2 Soluphor P R
  • polyoxyethylene-660-hydroxystearate Solutol HS 15 R
  • polyvinyl-pyrrolidon polyvinyl-pyrrolidon
  • the eye-drops according to our invention cause no eye-irritation by a 14 days treatment as it has been proved by animal experiments carried out on New Zealand rabbits.
  • the eye-drops according to the invention may contain beside the primycin known antimicrobic active ingredients as norfloxacin, pefloxacin, cyprofloxacin, ofloxacin too.
  • compositions according to the invention are illustrated by the following Example.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Ophthalmology & Optometry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Saccharide Compounds (AREA)

Abstract

The invention relates to an eye-drop, characterized by, that it contains, 0,02 - 0,1 mass % of primycin, 15,0 - 25,0 mass % of pyrrolidon-2, 12,0 - 25,0 mass % of polyoxyethylene-660-hydroxystearate, 1,0 - 5,0 mass % of polyvinyl-pyrrolidon and distilled water to complete to 100 mass percent.

Description

  • The invention relates to a stable aqueous solution containing as active ingredient primycin.
  • Subjects of the present invention are further therapeutical compositions prepared from the stable aqueous solution.
  • Primycin is a macrolide antibiotic agent, which is characterized in the literature (J. Chem. Soc. Perkin I. 1974, p. 816) by a single formula:
    /5-(18-(α-D-arabinofuranosyloxy)-2-butyl-3,7,11,15,19,21,23,25,27-nonahydroxy-4,16,32,34-tetramethyl-1-oxo-oxacyclohexatriakonta-16,32-diene-35-yl-)/4-hydroxyhexyl/guanidium-sulphate.
    Although the above literature describes its structure by a single formula, it is known, that it is an antibiotic-mixture consisting of several components (Hungarian Applications No. 2125/84 and 2869/84).
  • Primycin is a natural antibiotic agent originating from the fungal strain culture Thermopolyspora galeriensis, its preparation via fermentation is described in the Hungarian Patent Specification No. 153.593. Primycin is an antibiotic agent of a large spectrum, and it is firstly effective against gram positive bacteria and against polyresistent humanpathogenic strains too.
  • Primycin can be effectively applied for the treatment of epithelium lesions, in the urology, surgery, gynecology, dermatology, in the case of household lesions and for the treatment of burns respectively.
  • In the course of its application neither resistance nor, allergic reactions were experienced.
  • There are known further combinations of primycin with other antibiotics (Hungarian Patent Specification No. 158.241).
  • Although primycin is a very effective antibiotic, its therapeutical utilization was made extraordinarily difficult since it is practically insoluble in water.
    Thus, several efforts had earlier been made to eliminate these difficulties and to prepare pharmaceutical compositions containing primycin in a therapeutically well utilizable form while maintaining its efficiency as a whole.
  • The Hungarian Patent Specification No. 173.708 publishes heterocolloidal therapeutical compositions containing primycin. Their disadvantage is the low primycin content (0.2-1.0 %). Further the ethyl alcohol used for the preparation of the heterocolloidal solution has in some cases skin irritating effect and in the case the alcohol is vaporized from the treated surface one part of the primycin is running down from the skin without exerting a biological effect. This formulation cannot be used to prepare eye-drops.
  • The Hungarian Patent Specification No. 194.493 describes a basic gel containing primycin and N-methyl-pyrrolidon from which therapeutical compositions and different gels were prepared. This composition having a gel consistency is useful to incorporate the active ingredient practically in all qalenic forms such as ointments, creams or foams, however it is not useful to prepare eye-drops.
  • The aim of our invention was to prepare a stable aqueous solution containing primycin as active ingredient, which is free from alcohol and does not contain eye-irritating substances and this way it is suitable for the preparation of eye-drops.
  • According to the facts set forth above the invention relates to eye-drops characterized by, that they contain
    0,02 - 0,1 mass % of primycin,
    15,0 - 25,0 mass % of pyrrolidon,
    12,0 - 25,0 mass % of polyoxyethylene-660-hydroxystearate,
    1,0 - 5,0 mass % of polyvinyl-pyrrolidon and
    distilled water needed to complete to 100 mass %.
  • The eye-drops according to the invention are prepared in a way, that primycin is dissolved by heating in pyrrolidon-2 (Soluphor PR) and to the warm solution the polyoxyethylene-660-hydroxystearate (Solutol HS 15R) and polyvinyl-pyrrolidon are added. The distilled water is added to the system while stirring quickly and the solution is cooled to room-temperature while stirring.
  • The eye-drops according to our invention cause no eye-irritation by a 14 days treatment as it has been proved by animal experiments carried out on New Zealand rabbits.
  • The eye-drops according to the invention may contain beside the primycin known antimicrobic active ingredients as norfloxacin, pefloxacin, cyprofloxacin, ofloxacin too.
  • The compositions according to the invention are illustrated by the following Example.
    • EXAMPLE
  • An eye-drop with the following composition is prepared
    • Primycin
    0,05 mass %
    Soluphor PR
    20,0 mass %
    Soluptol HSR
    15,0 mass %
    Polyvinyl-pyrrolidon
    3,0 mass %
    Distilled water ad.
    100,0 mass %

Claims (2)

  1. Eye-drop, characterized by, that it contains
    0,02 - 0,1 mass % of primycin
    15,0 - 25,0 mass % of pyrrolidon-2
    12,0 - 25,0 mass % of polyoxyethylene-660-hydroxystearate
    1,0 - 5,0 mass % of polyvinyl-pyrrolidon
    and distilled water to complete to 100 mass percents.
  2. Eye-drop according to claim 1, characterized by, that it contains
    0,05 mass % of primycin
    20,0 mass % of pyrrolidon-2
    15,0 mass % of polyoxyethylene-660-hydroxystearate
    3,0 mass % of polyvinyl-pyrrolidon
    and distilled water to complete to 100 mass percents.
EP91903310A 1990-02-15 1991-02-08 Eye-drop Expired - Lifetime EP0474800B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT91903310T ATE99947T1 (en) 1990-02-15 1991-02-08 EYE DROP.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU90808A HU207222B (en) 1990-02-15 1990-02-15 Process for producing eyedrops containing primycin
HU80890 1990-02-15

Publications (2)

Publication Number Publication Date
EP0474800A1 EP0474800A1 (en) 1992-03-18
EP0474800B1 true EP0474800B1 (en) 1994-01-12

Family

ID=10951455

Family Applications (1)

Application Number Title Priority Date Filing Date
EP91903310A Expired - Lifetime EP0474800B1 (en) 1990-02-15 1991-02-08 Eye-drop

Country Status (11)

Country Link
EP (1) EP0474800B1 (en)
CN (1) CN1054718A (en)
AU (1) AU7210091A (en)
CA (1) CA2058949A1 (en)
CS (1) CS38191A2 (en)
DE (1) DE69100987D1 (en)
ES (1) ES2062764T3 (en)
FI (1) FI920461A0 (en)
HU (1) HU207222B (en)
IL (1) IL97159A0 (en)
WO (1) WO1991012008A1 (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1057444C (en) * 1994-03-16 2000-10-18 吴生武 Eyedrops for curing myopia
WO1996014079A1 (en) 1994-11-03 1996-05-17 Arzneimittelwerk Dresden Gmbh Novel cyclosporine preparation forms for oral administration of simple composition and high bio-availability, and process for producing them
DE19549852B4 (en) * 1995-11-29 2009-06-04 Novartis Ag Cyclosporin containing preparations
DE69716769T2 (en) * 1997-04-04 2003-06-12 Human Oltoanyagtermeloe Es Gyogyszergyarto Rt., Goedoelloe PREPARATIONS FOR THE TREATMENT OF BURNS AND EXTERNAL ULCERA AND METHOD FOR THE PRODUCTION THEREOF
FR2918891B1 (en) * 2007-07-20 2009-09-25 Thea Sa Lab OPHTHALMIC SOLUTION BASED ON PROSTAGLANDINS WITHOUT PRESERVATIVE
CA2898644A1 (en) * 2013-01-24 2014-07-31 Rigel Pharmaceuticals, Inc. Composition for ophthalmic administration

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1340517A (en) * 1969-12-01 1973-12-12 Burton Parsons Chemicals Inc Ophthalmic solution
GB1538903A (en) * 1975-04-11 1979-01-24 Nelson Res & Dev Carrier for a topically applied physiologically active agent or cosmetic agent
HU173708B (en) * 1975-06-20 1979-07-28 Chinoin Gyogyszer Es Vegyeszet Process for producing heterocolloide 18-arabinozil-2-n-butil-3,7,11,15,19,21,23,27,25,37-decahydroxy-4,16,32,34,36-pentamethyl-tetraconta-16,32-diene-35-0-lactone-40-guanidinium-sulfate
DE3104282A1 (en) * 1981-02-07 1982-10-28 Chinoin Gyógyszer és Vegyészeti Termékek Gyára RT, 1045 Budapest Therapeutic product with synergistic anti-microbial activity, and a process for the preparation thereof
CA1274508A (en) * 1984-05-31 1990-09-25 Imre Szilagyi Primycin components and process for the separation of the antibiotic complex
HU194493B (en) * 1985-11-27 1988-02-29 Chinoin Gyogyszer Es Vegyeszet Process for preparing primycin-containing colloidal basic gel and compositions comprising the same

Also Published As

Publication number Publication date
CS38191A2 (en) 1991-09-15
AU7210091A (en) 1991-09-03
CN1054718A (en) 1991-09-25
CA2058949A1 (en) 1991-08-16
ES2062764T3 (en) 1994-12-16
EP0474800A1 (en) 1992-03-18
HUT57047A (en) 1991-11-28
WO1991012008A1 (en) 1991-08-22
DE69100987D1 (en) 1994-02-24
HU900808D0 (en) 1990-04-28
FI920461A0 (en) 1992-02-03
IL97159A0 (en) 1992-08-18
HU207222B (en) 1993-03-29

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